Human cytomegalovirus is a ubiquitous herpesvirus that infects greater than 80 percent of the human population. Like all herpesviruses, HCMV is capable of establishing a life-long infection following primary exposure to the virus. Although HCMV infection is usually subclinical in healthy individuals, it is a major health problem for newborns and immunocompromised individuals. HCMV is the most common cause of congenital viral infection in the United States occurring in approximately 1 percent of all newborn infants. These congentital infections often result in sever mental and motor abnormalities. The other group of individuals frequently affected by HCMV are immunocompromised individuals, such as AIDS patients and transplant recipients. For example, HCMV is the primary cause of death in over 25 percent of AIDS patients, and is the single most important infectious agent affecting organ recipients. At least two-thirds of organ recipients develop a HCMV infection after transplantation, which often results in organ rejection. The increasing use of therapeutic immunosuppression, organ transplantation, and the incidence of AIDS, have focused attention upon the HCMV life cycle. The goal of the research in this proposal is to provide a better understanding of HCMV replication and specifically, characterize viral transcripts that are packaged within HCMV virions. This proposal is designed to investigate one of these virion transcripts, UL21.5. Three objectives have been outlined; 1) identify and characterize the protein product encoded by the UL21.5 virion RNA, 2) investigate the mechanism by which UL21.5 RNA is targeted to HCMV virions, and 3) determine if UL21.5 expression is required for HCMV replication in cultured cells. By understanding why and how HCMV packages viral transcripts within virions, novel approaches or theraputics may be identified to help combat HCMV infection.